PB2019: EFFICACY AND SAFETY OF IXAZOMIB PLUS LENALIDOMIDE AND DEXAMETHASONE FOLLOWING INJECTABLE PROTEASOME INHIBITOR-BASED THERAPY IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: M. Sasaki, K. Suzuki, Y. Abe, S. Ito, K. Nishiwaki, H. Handa, T. Chou, J. Soeda, I. Mori, T. Shinozaki, N. Takezako
Journal: HemaSphere (2022)

Background: Long-term proteasome inhibitor (PI)-based therapy improves outcomes in multiple myeloma (MM). However, physical, social, and geographic access to health services and treatment toxicity may interfere with long-term PI therapy in clinical practice. Aims: To evaluate the efficacy and safety of treatment with the oral PI, ixazomib (IXA), lenalidomide (LEN) + dexamethasone (DEX) [IRd] in patients with relapsed/refractory MM (RRMM) initially treated with an injectable PI-based therapy. Methods: Nationwide, multicenter, open-label, single-arm study in Japan. Patients aged ≥20 years with RRMM (including those not refractory to bortezomib (BOR), carfilzomib (CFZ), or LEN who provided written informed consent were enrolled. Patients received BOR, LEN + DEX (VRd), or CFZ, LEN + DEX (KRd) for 3 cycles. Patients with at least a minor response to VRd or KRd transitioned to IRd. After transition, patients received 4 mg IXA on days 1, 8, and 15, 25 mg LEN on days 1 through 21, + 40 mg DEX on days 1, 8, 15, and 22 in 28-day cycles until progressive disease (PD) or unacceptable toxicity. The primary endpoint was the 12-month progression-free survival (PFS) rate from the start of injectable PI-based therapy, with dropouts, missing response data, PD, and death at 12-month included as events. Secondary endpoints included PFS with dropouts treated as censoring (Kaplan-Meier [KM] method), overall survival (OS), overall response rate (ORR), percentage of patients with very good partial response (VGPR) or better, healthcare resource utilization, time to next treatment (TTNT), and safety. Results: Forty-five RRMM patients were enrolled, 36 of whom achieved minor response or better after 3 cycles of VRd (n=6) or KRd (n=30) and received IRd, and followed up for at least 12 months after the last patient startedinjectable PI-based therapy. Mean age was 70.7 (SD±9.2) years, the median (min, max) number of prior lines of therapy was 2 (1, 4), and 95.6% had an ECOG PS of 0−1. At a median follow-up of 20.8 (95% CI: 17.4-23.7) months, the 12-month PFS rate (primary endpoint) was 48.9% (22/45, 90% CI: 35.9−62.0) with 11 events of PD/death, 8 dropouts, and 4 missing response data, which exceeded the threshold of 36% but did not meet significance (p=0.0518). As secondary endpoints, the 12-month PFS rate (dropouts as censoring) by KM analysis was 74% (95% CI: 56−86). Median PFS and TTNT were 29.0 (95% CI: 21.3−NE) months and 32.3 (95% CI: 14.9−35.4) months, respectively; median OS was not estimable. The ORR was 73.3% (95% CI: 58.1−85.4) and 42.2% (95% CI: 27.7−57.8) of patients had a VGPR or better. The length of hospital stay, and outpatient visits during the initially 3 cycles of injectable PI-based treatment and following IRd treatment were 5.3 vs 1.0 days per person-month, and 4.2 vs 1.9 visits per person-month, respectively. The safety profile of IRd was similar and consistent to that previously reported. Frequent (≥10% incidence) Grade ≥3 treatment emergent adverse events were neutrophil count decreased (n=7 [15.6%]) and platelet count decreased (n=7 [15.6%]); the only SAE with a ≥10% incidence was pneumonia (n=5 [11.1%]). Two deaths occurred during the study, one during KRd treatment (pneumonia, bacterial, n=1 [2.2%]) and one during IRd treatment (pneumonia, n=1 [2.2%]), which was related to IRd. Summary/Conclusion: Long-term treatment with the oral PI, IXA, + LEN and DEX after an injectable PI-based treatment was tolerable and had favorable efficacy in patients with RRMM in the real-world setting.